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Gentian

Scientific Name(s): Gentiana acaulis L., Gentiana lutea L., Gentiana scabra Bunge.
Common Name(s): Bitter root, Bitterwort, Felwort, Gall weed, Gentian, Gentiana, Radix Gentianae Lutea

Clinical Overview

Use

No clinical trials support traditional use of gentian to stimulate appetite, improve digestion, or treat GI complaints. Gentian has also been used as an emmenagogue and to treat wounds, sore throat, arthritic inflammation, and jaundice.

Dosing

Infusions, decoctions, and macerations of gentian roots and rhizomes have been used as a bitter digestive tonic in doses of 1 to 4 g/day. There are no clinical studies to substantiate this dosage recommendation.

Contraindications

Contraindicated in gastric or duodenal ulcer and hypertension.

Pregnancy/Lactation

Documented adverse effects. Avoid use.

Interactions

None well documented.

Adverse Reactions

The extract may cause headache, nausea, and vomiting.

Toxicology

Mutagenicity has been demonstrated for methanolic extracts in Salmonella assays. Acute veratrum alkaloid poisoning has been reported due to accidental contamination of gentian preparations by veratrum.

Botany

Native to the mountains of central and southern Europe, G. lutea is a perennial herb that grows to 1.8 m with erect stems and smooth, oval leaves. The plant produces a cluster of fragrant orange-yellow flowers. The roots and rhizomes are nearly cylindrical, sometimes branched, varying in thickness from 5 to 40 mm. The root and rhizome portions are longitudinally wrinkled. The color of the rhizomes, ranging from dark brown to light tan, appears to be related to the content of bitter principles, because the darker roots have a more persistent, bitter taste. The roots and rhizomes of G. lutea are used medicinally.Meyer 1934, PLANTS 2010, WHO 1999

G. acaulis is a smaller herb with a basal rosette of lance-shaped leaves and generally grows to 10 cm in height. It is native to the European Alps at 914 to 1,524 m above sea level. The entire G. acaulis plant is used medicinally. Numerous species of gentian native to China are used in Chinese traditional medicine. Radix Gentianae Scabrae (known as Chinese or Japanese gentian) is indigenous to Korea, China, and Japan, and contains chemical constituents similar to these of G. lutea.WHO 1999

History

The gentians have been used for centuries as bitters to stimulate the appetite, improve digestion, and treat a variety of GI complaints (eg, diarrhea, heartburn, stomach ache, vomiting). Stemless gentian usually is consumed as a tea or alcoholic extract, such as Angostura bitters. The extracts are used in a variety of foods, cosmetics, and some antismoking products. The plant has been used externally to treat wounds and internally to treat sore throat, arthritic inflammation, and jaundice. Despite the name, the dye gentian violet is not derived from this plant.DerMarderosian 1988, Leung 1996, WHO 1999

Chemistry

The most characteristic aspect of gentian is its bitter taste imparted by a number of iridoid glycosides, primarily amarogentin, gentiopicrin (about 1.5% in fresh roots), gentiopicroside, and swertiamarin. The speed of drying of the roots affects their properties as medicinal bitters. Slow drying permits enzymatic hydrolysis of gentiopicrin into gentiogenin and glucose, therefore reducing bitterness. Gentian extract is used as a bitter in concentrations of approximately 0.02% in nonalcoholic beverages. The iridoids have been analyzed by thin-layer chromatography, micellar electrokinetic capillary chromatography, and high-performance liquid chromatography mass spectrometry.Bricout 1974, Glatz 2000, Szucs 2002

In addition to iridoids, the roots contain xanthones and triterpenes.Hayashi 1988, Kakuda 2003, Toriumi 2003 The reported pyridine alkaloids gentianine and gentialutine are thought to be artifacts of basic extraction derived from the iridoids. Stemless gentian also contains the xanthone glycoside gentiacauloside. The flowers and leaves of G. lutea contain iridoids, flavonoids, and xanthones.Menkovic 2000

Uses and Pharmacology

Quality clinical trials evaluating the effect of gentian or its chemical constituents are lacking.WHO 1999

Analgesic/anti-inflammatory

Animal data

Gentianine and gentiopicroside have been shown to exert a measurable anti-inflammatory and analgesic effect in animals. Extracts of G. lutea were active in carageenan-induced rat paw edema, xylol-induced mouse ear edema, and cotton-pellet granulatoma models. In addition, the extracts were active in several wound-healing models.Chen 2008, Mathew 2004, Ozturk 2006

Clinical data

Clinical trials are lacking.

Antimicrobial

Radix Gentianae Lutea and gentian extracts have been shown to exert antibacterial, antifungal, and antiprotozoal effects in vitro.WHO 1999

Methanolic extracts of the flowers and leaves of G. lutea demonstrated a wide range of activity against gram-positive and gram-negative bacteria and yeasts. Isolated chemical constituents mangiferin, isogentisin, and gentiopicrin also demonstrated activity.Savikin 2009, Weckesser 2007 Activity against Helicobacter pylori has been demonstrated in vitro.Lans 2007, Mahady 2005 Amarogentin and 2 other iridoids inhibited topoisomerase I of Leishmania.Ray 1996

Animal data

The roots of G. lutea have been used as an anthelmintic in ethnoveterinary medicine.Lans 2007

Clinical data

Clinical trials are lacking.

Hepatic effects

Animal data

In rats, intragastric and intraduodenal administration of gentian extracts stimulated bile productionLiu 2002, WHO 1999 and showed a protective effect on the liver against chemical insults.Liu 2002

Clinical data

In an uncontrolled study, stimulation of gall bladder secretions was increased by gentian.WHO 1999

GI tract

Bitter substances ingested before meals are reputed to improve the appetite and aid digestion by stimulating the flow of gastric juices and bile. However, because gentian is most often consumed in alcoholic beverages, it is difficult to distinguish the effects of gentian from those of alcohol.

Animal data

Ethanol extracts of the roots and rhizomes of G. lutea have increased gastric secretions in rats and sheep.WHO 1999

Clinical data

In 2 uncontrolled clinical studies, stimulation of gastric secretions was increased and GI symptoms (eg, abdominal pain, constipation, dyspepsia, heartburn) were reduced.WHO 1999

Other uses

Gentian extracts have hydroxy radical scavenging activityCalliste 2001, Kusar 2006 and exert a protective effect against ketoconazole-induced testicular damage in rats, assumed to be due to antioxidant effects.Amin 2008 Gentiopicroside and the essential oil of G. lutea relax smooth muscle in isolated animal trachea and ileum.Rojas 2000, WHO 1999 Gentian extracts prolong swimming endurance in mice.Öztürk 2002

Dosing

The pharmacokinetics and tissue distribution of gentiopicroside after oral and parenteral administration have been studied in mice. It was rapidly absorbed with low bioavailability and rapidly cleared.Wang 2004, Wang 2007

Infusions, decoctions, and macerations of gentian roots and rhizomes have been used as a bitter digestive tonic in doses of 1 to 4 g/day. There are no clinical studies to substantiate this dosage recommendation.WHO 1999

Pregnancy / Lactation

Mutagenic activity has been demonstrated in assays, and G. lutea has been traditionally used as an emmenagogue. Avoid use in pregnancy and lactation.WHO 1999

Interactions

Case reports are lacking; however, hemostatic activity has been demonstrated in vitro for extracts of G. luteaBakuridze 2009 and isogentisin and several other compounds from gentian inhibited monoamine oxidase.Suzuki 1978, Haraguchi 2004 If substantiated in a clinical setting, these properties may have implications for coadministration of anticoagulant or antidepressant medicines.

Adverse Reactions

The extract is usually taken in very small doses that do not appear to cause adverse effects; however, it may cause GI irritation, resulting in nausea and vomiting and, rarely, headache. Radix Gentianae Lutea is contraindicated in GI or duodenal ulcer. Classical texts include hypertension as a contraindication, but the reasons are difficult to substantiate.WHO 1999

Toxicology

Mutagenicity has been demonstrated for methanolic extracts in Salmonella assays.WHO 1999

The highly toxic white hellebore (Veratrum album L.) often grows in close proximity to gentian. Cases of acute veratrum alkaloid poisoning have been reported due to accidental contamination of gentian preparations by veratrum. Identification of esteralkaloids were the suspected cause of resulting nausea, vomiting, oral paraesthesia, hypotension, and severe bradycardia.Garnier 1985, Grobusch 2008, Rauber-Lüthy 2010

References

Amin A. Ketoconazole-induced testicular damage in rats reduced by Gentiana extract. Exp Toxicol Pathol. 2008;59(6):377-384.18222659
Bakuridze AD, Nikolaev SM, Tsagarenshvili NT, Kurdiani NG, Mikaia GA. Influence of Gentiana lutea L extract on blood coagulation [in Russian]. Georgian Med News. 2009;(172-173):89-91.19644199
Bricout J. Identification and determination of the bitter constituents of Gentiana lutea roots [in French]. Phytochemistry. 1974;13(12):2819-2823.
Calliste CA, Trouillas P, Allais DP, Simon A, Duroux JL. Free radical scavenging activities measured by electron spin resonance spectroscopy and B16 cell antiproliferative behaviors of seven plants. J Agric Food Chem. 2001;49(7):3321-3327.11453770
Chen L, Liu JC, Zhang XN, et al. Down-regulation of NR2B receptors partially contributes to analgesic effects of Gentiopicroside in persistent inflammatory pain. Neuropharmacology. 2008;54(8):1175-1181.18410946
DerMarderosian A, Liberti L. Natural Product Medicine. Philadelphia, PA: GF Stickley Co; 1988.
Garnier R, Carlier P, Hoffelt J, Savidan A. Acute dietary poisoning by white hellebore (Veratrum album L.). Clinical and analytical data. A propos of 5 cases [in French]. Ann Med Interne (Paris). 1985;136(2):125-128.4073696
Gentiana lutea L. USDA, NRCS. 2010. The PLANTS Database (http://plants.usda.gov, July 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA.
Glatz Z, Pospisilova J, Musil P. Determination of gentiopicroside in extracts of Centaurium erythreae and Gentiana lutea by micellar electrokinetic capillary chromatography. J Liq Chromatogr Relat Technol. 2000;23(12):1831-1839.
Grobosch T, Binscheck T, Martens F, Lampe D. Accidental intoxication with Veratrum album. J Anal Toxicol. 2008;32(9):768-773.19021933
Hayashi T, Yamagishi T. Two xanthone glycosides from Gentiana lutea. Phytochemistry. 1988;27(11):3696-3699.
Haraguchi H, Tanaka Y, Kabbash A, Fujioka T, Ishizu T, Yagi A. Monoamine oxidase inhibitors from Gentiana lutea. Phytochemistry. 2004;65(15):2255-2260.15587710
Kakuda R, Machida K, Yaoita Y, Kikuchi M, Kikuchi M. Studies on the constituents of Gentiana species. II. A new triterpenoid, and (S)-(+)- and (R)-(−)-gentiolactones from Gentiana lutea. Chem Pharm Bull (Tokyo). 2003;51(7):885-887.12843605
Kusar A, Zupancic A, Sentjurc M, Baricevic D. Free radical scavenging activities of yellow gentian (Gentiana lutea L.) measured by electron spin resonance. Hum Exp Toxicol. 2006;25(10):599-604.17165626
Lans C, Turner N, Khan T, Brauer G. Ethnoveterinary medicines used to treat endoparasites and stomach problems in pigs and pets in British Columbia, Canada. Vet Parasitol. 2007;148(3-4):325-340.17628343
Leung AY. Encyclopedia of Common Natural Ingredients Used in Food, Drugs, and Cosmetics. 2nd ed. New York, NY: J Wiley; 1996.
Liu ZW, Chen C, Jin R, Shi G, Song C, Hu Z. Studies on liver-protecting and bile secretion-promoting effects of gentiopicroside. Zhong Cao Yao. 2002;33:47-50.
Mahady GB, Pendland SL, Stoia A, et al. In vitro susceptibility of Helicobacter pylori to botanical extracts used traditionally for the treatment of gastrointestinal disorders. Phytother Res. 2005;19(11):988-991.16317658
Mathew A, Taranalli AD, Torgal SS. Evaluation of anti-inflammatory and wound healing activity of Gentiana lutea rhizome extract in animals. Pharm Biol. 2004;42(1):8-12.
Menkovic N, Savikin-Fodulovic, Savin K. Chemical composition and seasonal variations in the amount of secondary compounds in Gentiana lutea leaves and flowers. Planta Med. 2000;66(2):178-180.10763597
Meyer JE. The Herbalist. Hammond, IN: Hammond Book Co; 1934.
Öztürk N, Baser KH, Aydin S, Öztürk Y, Calis I. Effects of Gentiana lutea ssp. symphyandra on the central nervous system in mice. Phytother Res. 2002;16(7):627-631.12410542
Ozturk N, Korkmaz S, Ozturk Y, Baser KH. Effects of gentiopicroside, sweroside and swertiamarine, secoiridoids from gentian (Gentiana lutea ssp. symphyandra), on cultured chicken embryonic fibroblasts. Planta Med. 2006;72(4):289-294.16557467
Radix Gentianae Luteae. In: WHO Monographs on Selected Medicinal Plants. Vol 13. Geneva, Switzerland: World Health Organization; 1999.
Ray S, Majumder HK, Chakravarty AK, Mukhopadhyay S, Gil RR, Cordell GA. Amarogentin, a naturally occurring secoiridoid glycoside and a newly recognized inhibitor of topoisomerase I from Leishmania donovani. J Nat Prod. 1996;59(1):27-29.8984149
Rauber-Lüthy C, Halbsguth U, Kupferschmidt H, et al. Low-dose exposure to Veratrum album in children causes mild effects—a case series. Clin Toxicol (Phila). 2010;48(3):234-237.20170391
Rojas A, Bah M, Rojas JI, Gutiérrez DM. Smooth muscle relaxing activity of gentiopicroside isolated from Gentiana spathacea. Planta Med. 2000;66(8):765-767.11199140
Savikin K, Menkovic N, Zdunic G, Stevic T, Radanovic D, Jankovic T. Antimicrobial activity of Gentiana lutea L. extracts. Z Naturforsch C. 2009;64(5-6):339-342.19678535
Suzuki O, Katsumata Y, Oya M. Inhibition of monoamine oxidase by isogentisin and its 3-O-glucoside. Biochem Pharmacol. 1978;27(16):2075-2078.718732
Szucs Z, Danos B, Nyiredy S. Comparative analysis of the underground parts of Gentiana species by HPLC with diode-array and mass spectrometric detection. Chromatographia. 2002;56(1):S19-S23.
Toriumi Y, Kakuda R, Kikuchi M, Yaoita Y, Kikuchi M. New triterpenoids from Gentiana lutea. Chem Pharm Bull (Tokyo). 2003;51(1):89-91.12520135
Weckesser S, Engel K, Simon-Haarhaus B, Wittmer A, Pelz K, Schempp CM. Screening of plant extracts for antimicrobial activity against bacteria and yeasts with dermatological relevance. Phytomedicine. 2007;14(7-8):508-516.17291738
Wang CH, Wang ZT, Bligh SW, White KN, White CJ. Pharmacokinetics and tissue distribution of gentiopicroside following oral and intravenous administration in mice. Eur J Drug Metab Pharmacokinet. 2004;29(3):199-203.15537172
Wang CH, Cheng XM, He YQ, et al. Pharmacokinetic behavior of gentiopicroside from decoction of Radix Gentianae, Gentiana macrophylla after oral administration in rats: a pharmacokinetic comparison with gentiopicroside after oral and intravenous administration alone. Arch Pharm Res. 2007;30(9):1149-1154.17958334

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This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

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